Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of human Burkitts lymphoma cell lines treated with trichostatin A vs controls


ABSTRACT: Histone acetylation alters the chromatin state and thus gene expression and cellular activities. In spite of various applications of Histone Deacetylase inhibitors (DACIs) their mechanism or selectivity is not fully understood. We studied the mechanism by which the DACI Trichostatin A upregulates the MHC class II DRA gene in RJ225 cells lacking CIITA. We show that TSA increases HDAC1 and 2 protein mobility and reduces their recruitment to the DRA promoter. Coordinated chromatin changes are manifested by increasing H3 K4 methylation and decreasing K9 methylation, leading to elevated RNA PolII recruitment and the onset of transcription. Gene expression profiling showed that diverse TSA responsive gene groups, including the highly upregulated the MHC class II family and the adjacent histone cluster are located in chromosome 6p21-22. A complex pattern of gene reprogramming by TSA involves immune recognition, antiviral, apoptotic and inflammatory pathways and extends the rationale for using DACIs to modulate the immune response.

ORGANISM(S): Homo sapiens

SUBMITTER: Joseph Papamatheakis 

PROVIDER: E-MEXP-403 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Coordinated changes of histone modifications and HDAC mobilization regulate the induction of MHC class II genes by Trichostatin A.

Gialitakis Manolis M   Kretsovali Androniki A   Spilianakis Charalampos C   Kravariti Lara L   Mages Jörg J   Hoffmann Reinhard R   Hatzopoulos Antonis K AK   Papamatheakis Joseph J  

Nucleic acids research 20060201 3


The deacetylase inhibitor Trichostatin A (TSA) induces the transcription of the Major Histocompatibility Class II (MHC II) DRA gene in a way independent of the master coactivator CIITA. To analyze the molecular mechanisms by which this epigenetic regulator stimulates MHC II expression, we used chromatin immunoprecipitation (ChIP) assays to monitor the alterations in histone modifications that correlate with DRA transcription after TSA treatment. We found that a dramatic increase in promoter link  ...[more]

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